The saliva of blood-feeding parasites is a rich source of peptidase inhibitors that help to overcome the host's defence during host–parasite interactions. Using proteomic analysis, the cystatin OmC2 was demonstrated in the saliva of the soft tick Ornithodoros moubata, an important disease vector transmitting African swine fever virus and the spirochaete Borrelia duttoni. A structural, biochemical and biological characterization of this peptidase inhibitor was undertaken in the present study. Recombinant OmC2 was screened against a panel of physiologically relevant peptidases and was found to be an effective broad-specificity inhibitor of cysteine cathepsins, including endopeptidases (cathepsins L and S) and exopeptidases (cathepsins B, C and H). The crystal structure of OmC2 was determined at a resolution of 2.45 Å (1 Å=0.1 nm) and was used to describe the structure–inhibitory activity relationship. The biological impact of OmC2 was demonstrated both in vitro and in vivo. OmC2 affected the function of antigen-presenting mouse dendritic cells by reducing the production of the pro-inflammatory cytokines tumour necrosis factor α and interleukin-12, and proliferation of antigen-specific CD4+ T-cells. This suggests that OmC2 may suppress the host's adaptive immune response. Immunization of mice with OmC2 significantly suppressed the survival of O. moubata in infestation experiments. We conclude that OmC2 is a promising target for the development of a novel anti-tick vaccine to control O. moubata populations and combat the spread of associated diseases.
Skip Nav Destination
Article navigation
July 2010
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
June 14 2010
Crystal structure and functional characterization of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata
Jiří Salát;
Jiří Salát
1
*Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic, Branišovská 31, 37005 České Budějovice, Czech Republic
†Faculty of Sciences, University of South Bohemia, Branišovská 31, 37005 České Budějovice, Czech Republic
1Correspondence may be addressed to either of these authors (email george@paru.cas.cz or mares@uochb.cas.cz).
Search for other works by this author on:
Guido C. Paesen;
Guido C. Paesen
‡Centre for Ecology and Hydrology, Mansfield Road, Oxford OX1 3SR, U.K.
Search for other works by this author on:
Pavlína Řezáčová;
Pavlína Řezáčová
§Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 16610 Praha 6, Czech Republic
‖Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 16610 Praha 6, Czech Republic
Search for other works by this author on:
Michalis Kotsyfakis;
Michalis Kotsyfakis
*Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic, Branišovská 31, 37005 České Budějovice, Czech Republic
¶Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, U.S.A.
Search for other works by this author on:
Zuzana Kovářová;
Zuzana Kovářová
§Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 16610 Praha 6, Czech Republic
**Department of Biochemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 12843 Praha 2, Czech Republic
Search for other works by this author on:
Miloslav Šanda;
Miloslav Šanda
§Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 16610 Praha 6, Czech Republic
Search for other works by this author on:
Juraj Majtán;
Juraj Majtán
‡Centre for Ecology and Hydrology, Mansfield Road, Oxford OX1 3SR, U.K.
Search for other works by this author on:
Lenka Grunclová;
Lenka Grunclová
*Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic, Branišovská 31, 37005 České Budějovice, Czech Republic
†Faculty of Sciences, University of South Bohemia, Branišovská 31, 37005 České Budějovice, Czech Republic
Search for other works by this author on:
Helena Horká;
Helena Horká
*Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic, Branišovská 31, 37005 České Budějovice, Czech Republic
†Faculty of Sciences, University of South Bohemia, Branišovská 31, 37005 České Budějovice, Czech Republic
Search for other works by this author on:
John F. Andersen;
John F. Andersen
¶Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, U.S.A.
Search for other works by this author on:
Jiří Brynda;
Jiří Brynda
§Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 16610 Praha 6, Czech Republic
‖Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 16610 Praha 6, Czech Republic
Search for other works by this author on:
Martin Horn;
Martin Horn
§Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 16610 Praha 6, Czech Republic
Search for other works by this author on:
Miles A. Nunn;
Miles A. Nunn
‡Centre for Ecology and Hydrology, Mansfield Road, Oxford OX1 3SR, U.K.
Search for other works by this author on:
Petr Kopáček;
Petr Kopáček
*Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic, Branišovská 31, 37005 České Budějovice, Czech Republic
†Faculty of Sciences, University of South Bohemia, Branišovská 31, 37005 České Budějovice, Czech Republic
Search for other works by this author on:
Jan Kopecký;
Jan Kopecký
*Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic, Branišovská 31, 37005 České Budějovice, Czech Republic
†Faculty of Sciences, University of South Bohemia, Branišovská 31, 37005 České Budějovice, Czech Republic
Search for other works by this author on:
Michael Mareš
Michael Mareš
1
§Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 16610 Praha 6, Czech Republic
1Correspondence may be addressed to either of these authors (email george@paru.cas.cz or mares@uochb.cas.cz).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
February 22 2010
Revision Received:
April 21 2010
Accepted:
April 28 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 429 (1): 103–112.
Article history
Received:
February 22 2010
Revision Received:
April 21 2010
Accepted:
April 28 2010
Citation
Jiří Salát, Guido C. Paesen, Pavlína Řezáčová, Michalis Kotsyfakis, Zuzana Kovářová, Miloslav Šanda, Juraj Majtán, Lenka Grunclová, Helena Horká, John F. Andersen, Jiří Brynda, Martin Horn, Miles A. Nunn, Petr Kopáček, Jan Kopecký, Michael Mareš; Crystal structure and functional characterization of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata. Biochem J 1 July 2010; 429 (1): 103–112. doi: https://doi.org/10.1042/BJ20100280
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.